The current application requests support to create a Specialized Center of Research (SCOR) in Systemic Lupus Erythematosus at the University of North Carolina at Chapel Hill. Our proposal will unite seven investigators with previous strong backgrounds in SLE research (Drs. Eisenberg, Clarke, Cohen, Dooley, Falk, Reeves,and Winfield) in four projects directed at furthering our understanding of the immunoregulation of autoantibody production in SLE. We will investigate both human disease and murine models, and we will combine expertise in clinical research, cellular immunology, immunochemistry, immunogenetics, and the molecular biology of autoantibodies and autoantigens. An administrative core will support the overall direction of the SCOR (Dr. Eisenberg, Director, and Dr. Winfield, Assistant Director) and provide secretarial and accounting services for the four projects. The SCOR will receive support from the Division of Rheumatology, the Multipurpose Arthritis Center, and the Thurston Arthritis Center, and its functions will be efficiently integrated with these existent entities through their director, Dr. Winfield. The projects of the SCOR are: Project 1: Anti-Sm B Cells of MRL/lpr Mice," Dr. Clarke, PI, which will investigate the immunogenetics of autoantibody genes and the immunoregulation of the mice; Project 2: "Programmed Cell Death and Systemic Autoimmunity," Dr. Cohen, PI, which will investigate the role of apoptosis in self tolerance and in the release of autoantigens; Project 3: "Preserving Ovarian Function in Lupus Nephritis Therapy," Drs. Falk and Dooley, co-PIs, which will test whether chemically induced temporary menopause can protect against the sterilizing effects of cyclophosphamide therapy and downregulate active SLE; and Project 4: "Positive Feedback Regulation of Autoantibody Production," Dr. Reeves, PI, which will isolate genes for several autoantigens and investigate how antibodies to such proteins can be induced by other autoantibodies. The further understanding of the regulation of autoantibody production will eventually permit the design of specific therapies in human SLE.